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Frontiers in Oncology 2023Distant metastasis from rectal cancer usually results in poorer survival and quality of life, so early identification of patients at high risk of distant metastasis from...
BACKGROUND
Distant metastasis from rectal cancer usually results in poorer survival and quality of life, so early identification of patients at high risk of distant metastasis from rectal cancer is essential.
METHOD
The study used eight machine-learning algorithms to construct a machine-learning model for the risk of distant metastasis from rectal cancer. We developed the models using 23867 patients with rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. Meanwhile, 1178 rectal cancer patients from Chinese hospitals were selected to validate the model performance and extrapolation. We tuned the hyperparameters by random search and tenfold cross-validation to construct the machine-learning models. We evaluated the models using the area under the receiver operating characteristic curves (AUC), the area under the precision-recall curve (AUPRC), decision curve analysis, calibration curves, and the precision and accuracy of the internal test set and external validation cohorts. In addition, Shapley's Additive explanations (SHAP) were used to interpret the machine-learning models. Finally, the best model was applied to develop a web calculator for predicting the risk of distant metastasis in rectal cancer.
RESULT
The study included 23,867 rectal cancer patients and 2,840 patients with distant metastasis. Multiple logistic regression analysis showed that age, differentiation grade, T-stage, N-stage, preoperative carcinoembryonic antigen (CEA), tumor deposits, perineural invasion, tumor size, radiation, and chemotherapy were-independent risk factors for distant metastasis in rectal cancer. The mean AUC value of the extreme gradient boosting (XGB) model in ten-fold cross-validation in the training set was 0.859. The XGB model performed best in the internal test set and external validation set. The XGB model in the internal test set had an AUC was 0.855, AUPRC was 0.510, accuracy was 0.900, and precision was 0.880. The metric AUC for the external validation set of the XGB model was 0.814, AUPRC was 0.609, accuracy was 0.800, and precision was 0.810. Finally, we constructed a web calculator using the XGB model for distant metastasis of rectal cancer.
CONCLUSION
The study developed and validated an XGB model based on clinicopathological information for predicting the risk of distant metastasis in patients with rectal cancer, which may help physicians make clinical decisions. rectal cancer, distant metastasis, web calculator, machine learning algorithm, external validation.
PubMed: 37655097
DOI: 10.3389/fonc.2023.1235121 -
Cellular Oncology (Dordrecht) Feb 2024In recent years, the significance of the nervous system in the tumor microenvironment has gained increasing attention. The bidirectional communication between nerves and... (Review)
Review
BACKGROUND
In recent years, the significance of the nervous system in the tumor microenvironment has gained increasing attention. The bidirectional communication between nerves and cancer cells plays a critical role in tumor initiation and progression. Perineural invasion (PNI) occurs when tumor cells invade the nerve sheath and/or encircle more than 33% of the nerve circumference. PNI is a common feature in various malignancies and is associated with tumor invasion, metastasis, cancer-related pain, and unfavorable clinical outcomes. The colon and rectum are highly innervated organs, and accumulating studies support PNI as a histopathologic feature of colorectal cancer (CRC). Therefore, it is essential to investigate the role of nerves in CRC and comprehend the mechanisms of PNI to impede tumor progression and improve patient survival.
CONCLUSION
This review elucidates the clinical significance of PNI, summarizes the underlying cellular and molecular mechanisms, introduces various experimental models suitable for studying PNI, and discusses the therapeutic potential of targeting this phenomenon. By delving into the intricate interactions between nerves and tumor cells, we hope this review can provide valuable insights for the future development of CRC treatments.
Topics: Humans; Clinical Relevance; Colorectal Neoplasms; Neoplasm Invasiveness; Tumor Microenvironment
PubMed: 37610689
DOI: 10.1007/s13402-023-00857-y -
Current Oncology (Toronto, Ont.) Jul 2023Non-melanoma skin cancer of the head and neck (NMSCHN) is one of the most common malignancies worldwide, and its incidence is growing at a significant rate. It has been... (Review)
Review
Non-melanoma skin cancer of the head and neck (NMSCHN) is one of the most common malignancies worldwide, and its incidence is growing at a significant rate. It has been found to be aggressive in its spread and has the capacity to metastasize to regional lymph nodes. Cutaneous squamous cell carcinoma (cSCC) has a considerably high mortality rate. It has remarkable characteristics: diameter >2 cm, depth >5 mm, high recurrence, perineural invasion, and locoregional metastases. Aggressive cSCC lesions most commonly metastasize to the parotid gland. Also, immunocompromised patients have a higher risk of developing this aggressive cancer along with the worst prognostic outcomes. It is very important to discuss and assess the risk factors, prognostic factors, and outcomes of patients with cSCC, which will give clinicians future directives for making modifications to their treatment plans. The successful treatment of aggressive cSCC of the head and neck includes early detection and diagnosis, surgery alone or adjuvant chemotherapy, and radiotherapy as required. Multimodal therapy options should be considered by clinicians for better outcomes of aggressive cSCC of the head and neck.
Topics: Humans; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Skin Neoplasms; Head and Neck Neoplasms; Neoplasm Staging
PubMed: 37504347
DOI: 10.3390/curroncol30070487 -
International Journal of Molecular... Oct 2023Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive solid tumors with a dismal prognosis and an increasing incidence. At the time of diagnosis,... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive solid tumors with a dismal prognosis and an increasing incidence. At the time of diagnosis, more than 85% of patients are in an unresectable stage. For these patients, chemotherapy can prolong survival by only a few months. Unfortunately, in recent decades, no groundbreaking therapies have emerged for PDAC, thus raising the question of how to identify novel therapeutic druggable targets to improve prognosis. Recently, the tumor microenvironment and especially its neural component has gained increasing interest in the pancreatic cancer field. A histological hallmark of PDAC is perineural invasion (PNI), whereby cancer cells invade surrounding nerves, providing an alternative route for metastatic spread. The extent of PNI has been positively correlated with early tumor recurrence and reduced overall survival. Multiple studies have shown that mechanisms involved in PNI are also involved in tumor spread and pain generation. Targeting these pathways has shown promising results in alleviating pain and reducing PNI in preclinical models. In this review, we will describe the mechanisms and future treatment strategies to target this mutually trophic interaction between cancer cells to open novel avenues for the treatment of patients diagnosed with PDAC.
Topics: Humans; Tumor Microenvironment; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Pain
PubMed: 37834436
DOI: 10.3390/ijms241914989 -
International Journal of Surgery... Dec 2023To investigate the clinicopathological features and prognosis of synchronous and metachronous multiple primary colorectal cancer.
BACKGROUND
To investigate the clinicopathological features and prognosis of synchronous and metachronous multiple primary colorectal cancer.
MATERIALS AND METHODS
Patients who underwent operation for synchronous and metachronous colorectal cancer at the colorectal surgery department of Shanghai Changhai Hospital between January 2000 and December 2021 were included. Perioperative indicators were comprehensively compared and included in the survival analyses.
RESULTS
In total, 563 patients with synchronous ( n =372) and metachronous ( n =191) colorectal cancer were included. Patients with synchronous colorectal cancer were more likely to have a long onset time, positive carcinoembryonic antigen, advanced TNM stage, large tumor, perineural invasion, p53 high expression, and mismatch repair proficient. Compared with metachronous colorectal cancer, patients with synchronous colorectal cancer showed worse 5-year overall survival (68.6±3.0% vs 81.9±3.5%, P =0.018) and 5-year disease-free survival (61.2±3.1% vs 71.0±3.9%, P =0.022). In the subgroup analysis, segmental resection was an independent risk factor for the long-term outcomes of bilateral synchronous colorectal cancer.
CONCLUSIONS
Clinicopathological and molecular features were different between synchronous and metachronous colorectal cancer. Patients with synchronous colorectal cancer showed a worse prognosis than those with metachronous colorectal cancer. Bilateral synchronous colorectal cancer requires extended resection to achieve improved long-term outcomes.
Topics: Humans; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Retrospective Studies; Colorectal Neoplasms; China; Prognosis
PubMed: 37737848
DOI: 10.1097/JS9.0000000000000709 -
Journal of Anaesthesiology, Clinical... 2024Dexamethasone is routinely used in anesthesia practice and has been regarded as one of the ideal perioperative agents. It is a synthetic glucocorticoid with potent... (Review)
Review
Dexamethasone is routinely used in anesthesia practice and has been regarded as one of the ideal perioperative agents. It is a synthetic glucocorticoid with potent antiinflammatory action. It reduces postoperative nausea and vomiting, pain, postoperative opioid requirements after general anaesthesia as well as spinal anaesthesia. It has been used via intravenous, epidural and perineural routes. It has been used successfully in fascial blocks. It significantly decreases fatigue, shivering and postoperative sore throat and improves quality of recovery.
PubMed: 38666172
DOI: 10.4103/joacp.joacp_164_22 -
Clinical Cancer Research : An Official... Jul 2023Perineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive...
PURPOSE
Perineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive additional therapies after surgical resection. Mechanistic studies have shown that nerves in the tumor microenvironment promote aggressive tumor growth. Therefore, in this study, we evaluated whether nerve density (ND) influences tumor growth and patient survival. Moreover, we assessed the reliability of artificial intelligence (AI) in evaluating ND.
EXPERIMENTAL DESIGN
To investigate whether increased ND in OSCC influences patient outcome, we performed survival analyses. Tissue sections of OSCC from 142 patients were stained with hematoxylin and eosin and IHC stains to detect nerves and tumor. ND within the tumor bulk and in the adjacent 2 mm was quantified; normalized ND (NND; bulk ND/adjacent ND) was calculated. The impact of ND on tumor growth was evaluated in chick chorioallantoic-dorsal root ganglia (CAM-DRG) and murine surgical denervation models. Cancer cells were grafted and tumor size quantified. Automated nerve detection, applying the Halo AI platform, was compared with manual assessment.
RESULTS
Disease-specific survival decreased with higher intratumoral ND and NND in tongue SCC. Moreover, NND was associated with worst pattern-of-invasion and PNI. Increasing the number of DRG, in the CAM-DRG model, increased tumor size. Reduction of ND by denervation in a murine model decreased tumor growth. Automated and manual detection of nerves showed high concordance, with an F1 score of 0.977.
CONCLUSIONS
High ND enhances tumor growth, and NND is an important prognostic factor that could influence treatment selection for aggressive OSCC. See related commentary by Hondermarck and Jiang, p. 2342.
Topics: Humans; Animals; Mice; Artificial Intelligence; Reproducibility of Results; Neoplasm Invasiveness; Mouth Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Tumor Microenvironment
PubMed: 37039710
DOI: 10.1158/1078-0432.CCR-22-3496 -
Biochimica Et Biophysica Acta. Reviews... Nov 2023This review summarizes emerging evidence that the neuroendocrine system is involved in the regulation of the tumor immune microenvironment (TIME) to influence cancer... (Review)
Review
This review summarizes emerging evidence that the neuroendocrine system is involved in the regulation of the tumor immune microenvironment (TIME) to influence cancer progression. The basis of the interaction between the neuroendocrine system and cancer is usually achieved by the infiltration of nerve fibers into the tumor tissue, which is called neurogenesis; the migration of cancer cells toward nerve fibers, which is called perineural invasion (PNI), and the neurotransmitters. In addition to the traditional role of neurotransmitters in neural communications, neurotransmitters are increasingly recognized as mediators of crosstalk between the nervous system, cancer cells, and the immune system. Recent studies have revealed that not only nerve fibers but also cancer cells and immune cells within the TIME can secrete neurotransmitters, exerting influence on both neurons and themselves. Furthermore, immune cells infiltrating the tumor environment have been found to express a wide array of neurotransmitter receptors. Hence, targeting these neurotransmitter receptors may promote the activity of immune cells in the tumor microenvironment and exert anti-tumor immunity. Herein, we discuss the crosstalk between the neuroendocrine system and tumor-infiltrating immune cells, which may provide feasible cancer immunotherapy options.
Topics: Humans; Neoplasms; Neurosecretory Systems; Immunotherapy; Neurotransmitter Agents; Receptors, Neurotransmitter; Tumor Microenvironment
PubMed: 37907132
DOI: 10.1016/j.bbcan.2023.189007 -
Journal of Hand Surgery Global Online Jul 2023Carpal and cubital tunnel syndrome can cause debilitating pain and weakness in the hand and upper extremities. Although most patients have a resolution of their symptoms...
Carpal and cubital tunnel syndrome can cause debilitating pain and weakness in the hand and upper extremities. Although most patients have a resolution of their symptoms after primary decompression, managing those with recalcitrant neuropathies is challenging. The etiology of persistent, recurrent, or new symptoms is not always clear and requires careful attention to the history and physical examination to confirm the diagnosis or consider other causes prior to committing to surgery. Nevertheless, revision surgery is often needed in the setting of recalcitrant neuropathies in order to improve patients' symptoms. Revision surgery typically entails wide exposure and neurolysis to release residual compression. In addition, vascularized tissue and nerve wraps have been routinely used to create a favorable perineural environment that decreases recurrent scar formation. This review discusses the etiologies of recalcitrant upper extremity neuropathies, the current treatment options, and surgical outcomes.
PubMed: 37521539
DOI: 10.1016/j.jhsg.2023.03.002 -
Clinical Epigenetics Dec 2023Colon cancer (CC) is a heterogeneous disease that is categorized into four Consensus Molecular Subtypes (CMS) according to gene expression. Patients with loco-regional...
BACKGROUND
Colon cancer (CC) is a heterogeneous disease that is categorized into four Consensus Molecular Subtypes (CMS) according to gene expression. Patients with loco-regional CC (stages II/III) lack prognostic factors, making it essential to analyze new molecular markers that can delineate more aggressive tumors. Aberrant methylation of genes that are essential in crucial mechanisms such as epithelial mesenchymal transition (EMT) contributes to tumor progression in CC. We evaluate the presence of hyper- and hypomethylation in subrogate IHC markers used for CMS classification (CDX2, FRMD6, HTR2B, ZEB1) of 144 stage II/III patients and CC cell lines by pyrosequencing. ZEB1 expression was also studied in control and shRNA-silenced CC cell lines and in paired normal tissue/tumors by quantitative PCR. The pattern of ZEB1 staining was also analyzed in methylated/unmethylated tumors by immunohistochemistry.
RESULTS
We describe for the first time the hypermethylation of ZEB1 gene and the hypomethylation of the FRMD6 gene in 32.6% and 50.9% of tumors, respectively. Additionally, we confirm the ZEB1 re-expression by epigenetic drugs in methylated cell lines. ZEB1 hypermethylation was more frequent in CMS1 patients and, more importantly, was a good prognostic factor related to disease-free survival (p = 0.015) and overall survival (p = 0.006) in our patient series, independently of other significant clinical parameters such as patient age, stage, lymph node involvement, and blood vessel and perineural invasion.
CONCLUSIONS
Aberrant methylation is present in the subrogate genes used for CMS classification. Our results are the first evidence that ZEB1 is hypermethylated in CC and that this alteration is an independent factor of good prognosis.
Topics: Humans; Zinc Finger E-box-Binding Homeobox 1; DNA Methylation; Colonic Neoplasms; Prognosis; RNA, Small Interfering; Epithelial-Mesenchymal Transition; Biomarkers, Tumor
PubMed: 38093305
DOI: 10.1186/s13148-023-01605-7